(23 days)
Elecsys PreciControl TS is used for quality control of the Elecsys TSH immunoassay on the Elecsys and cobas e immunoassay analyzers.
The Elecsys PreciControl TS is a lyophilized product consisting of human TSH at a euthyroid level in an equine serum matrix. During manufacture, the analyte is spiked into the matrix at the desired concentration levels. All human material should be considered potentially infectious. All products derived from human blood are prepared exclusively from the blood of donors tested individually and shown to be free from HBsAg and antibodies to HCV and HIV. The testing methods applied were FDA-approved or cleared in compliance with the European Directive 98/79/EC, Annex II, List A.
This document describes the 510(k) submission for the Elecsys PreciControl TS, a quality control material for TSH immunoassays. The studies conducted focus on "Value Assignment," "Stability," and "Reconstitution" of the device.
Here's an analysis of the acceptance criteria and study information provided:
1. Table of Acceptance Criteria and Reported Device Performance
| Study Component | Acceptance Criteria | Reported Device Performance |
|---|---|---|
| Value Assignment | (a) Precision, % CV: For TSH target value of 0.2 µIU/mL, % CV ≤ 9. | |
| (b) Acceptance range of Assigned Value, [%]: For TSH target value of 0.2 µIU/mL, range 60-140%. | ||
| (c) Assigned value on Additional vs. Master Platform, %: For TSH target value of 0.2 µIU/mL, range 90-110%. | Conclusion: "Acceptance criteria for all stages of the process were met, supporting the target values and ranges above." Specific numerical results for each criterion are not provided in the summary but are stated to have passed. | |
| Stability (Reconstituted: 72 hours at 2-8°C, 5 hours on analyzers) | Recovery: 90-110% of the reference material value. | Table 3: Stability of Reconstituted Lyophilized PreciControl TS (72h at 2-8°C, then 6h at 20-25°C) |
| PC TS Sample: Reference 0.174 µIU/mL, Stressed control 0.168 µIU/mL. | ||
| % Recovery: 96.6% | ||
| Conclusion: "The data support the package insert claim that reconstituted PreciControl TS is stable for up to: 72 hours at 2-8°C, 5 h at 20-25°C on the analyzers." (The 5 hours on analyzers claim is implicit from the 6h at 20-25°C in the study description). | ||
| Stability (Reconstituted: 31 days at -20°C) | Recovery: 90-110% of the reference material value. | Table 4: Stability of Reconstituted Lyophilized on cobas e 411 (32 days at -20°C, then 6h at 20-25°C) |
| PC TS Sample: Reference 0.174 µIU/mL, Stressed control 0.177 µIU/mL. | ||
| % Recovery: 101.7% | ||
| Conclusion: "The data support the package insert claim that reconstituted PreciControl TS is stable for up to: 31 days at -20°C." | ||
| Real-Time Stability (Shelf Life) | Recovery: 90-110% of the unstressed reference value (stored at -20°C). | Table 5: Real-time Stability testing plan for PreciControl TS |
| The table shows % Recovery at various time points (months) for three lots (DR01, DR02, DR03). All reported values are within the 90-110% range. | ||
| Lot DR01: 6m (106%), 9m (100%), 12m (103%), 16m (99%), 19m (103%), 25m (102%) | ||
| Lot DR02: 6m (99%), 9m (100%), 12m (103%), 16m (98%), 19m (102%), 25m (102%) | ||
| Lot DR03: 6m (100%), 9m (99%), 12m (95%), 16m (99%), 19m (101%), 25m (99%) | ||
| Conclusion: "Data support the current package insert claim of shelf life of 24 months." (Note: Data up to 25 months is provided, supporting the 24-month claim). | ||
| Reconstitution Time Study | Recovery: 90-110% of the value obtained for the 30-minute reconstituted material. | Table showing Reconstitution Time Study |
| Reference (30 min) TS: 0.174 µIU/mL, On-Test (60 min) TS: 0.174 µIU/mL. | ||
| % Recovery: 100.0% | ||
| Conclusion: "The data support the package insert claim that the PreciControl TS is completely reconstituted after 30 minutes." |
2. Sample Size and Data Provenance (Test Set)
- Value Assignment:
- The controls are run in duplicate on at least three (3) MODULAR ANALYTICS E170 measuring cells.
- The assigned value is the median of at least six (6) determinations per control level.
- Data provenance: Not explicitly stated, but assumed to be internal laboratory testing by Roche Diagnostics. It would typically be prospective for a new product's value assignment.
- Stability Studies (Study 1 & 2):
- "The on-test and reference materials were tested in duplicate."
- "The PreciControl TS lot was evaluated in duplicate on the cobas e 411."
- Sample size for "stressed" and "reference" is one lot, with duplicate measurements.
- Data provenance: Internal laboratory testing by Roche Diagnostics, likely prospective for stability validation.
- Real-Time Stability Study (Study 3):
- "Data for the time-points at 6, 12, 16, 19, 25 and 37 months tested in duplicate will be available."
- "Currently, the shelf life claim is 24 months. This is based on real-time stability data of three lots."
- Sample size: Three lots tested in duplicate at various time points.
- Data provenance: Internal laboratory testing by Roche Diagnostics, prospective, ongoing.
- Reconstitution Time Study:
- "PreciControl TS was reconstituted for 30 minutes (reference) and 60 minutes. Samples were evaluated in duplicate on the cobas e 411 analyzer."
- Sample size: One lot used, with duplicate measurements at each time point.
- Data provenance: Internal laboratory testing by Roche Diagnostics, likely prospective.
3. Number of Experts and Qualifications for Ground Truth (Test Set)
This device is a quality control material for an immunoassay. The concept of "experts" and "ground truth" as typically applied to image-based diagnostic devices (e.g., radiologists interpreting images) is not directly applicable here.
- Value Assignment: The ground truth or "target value" for the TSH control material is established against the 2nd IRP WHO Reference Standard 80/558. This is a primary reference standard, not dependent on human expert interpretation.
- Stability and Reconstitution: Ground truth is against an unstressed reference material value or a value obtained under standard reconstitution conditions, measured by the same analytical equipment.
Therefore, no human experts are noted as establishing the ground truth for the performance studies of this quality control device.
4. Adjudication Method (Test Set)
Not applicable for this type of device and study. The measurements are quantitative and compared against established reference values or performance specifications, not subjective interpretations requiring adjudication.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
Not applicable. This device is a quality control material, not a diagnostic algorithm that assists human readers.
6. Standalone (Algorithm Only) Performance Study
This is a standalone performance study of the quality control material itself (Elecsys PreciControl TS) without human intervention in the result generation or interpretation by the device. The purpose is to characterize the performance of the control material (e.g., its target value, stability) when run on an automated immunoassay analyzer. The performance metrics are analytical (precision, recovery, stability), not diagnostic.
7. Type of Ground Truth Used
- Value Assignment: The ground truth for the analyte (TSH) concentration in the control material is traceable to the 2nd IRP WHO Reference Standard 80/558. This is a recognized international reference standard for TSH, providing a highly accurate and standardized basis for the assigned value.
- Stability and Reconstitution Studies: The ground truth for these studies is typically derived from reference measurements (e.g., freshly prepared material, material stored under optimal conditions, or material reconstituted according to the standard protocol). This involves comparing the "stressed" or "test" material's measurement against an unstressed or reference measurement using the same analytical method.
8. Sample Size for the Training Set
Not applicable. This is a quality control material, not an AI/ML algorithm that requires a "training set" in the conventional sense. The "value assignment" process and stability studies are for characterizing the product itself, not for training a model.
9. How the Ground Truth for the Training Set was Established
Not applicable, as no training set for an AI/ML algorithm is involved.
§ 862.1660 Quality control material (assayed and unassayed).
(a)
Identification. A quality control material (assayed and unassayed) for clinical chemistry is a device intended for medical purposes for use in a test system to estimate test precision and to detect systematic analytical deviations that may arise from reagent or analytical instrument variation. A quality control material (assayed and unassayed) may be used for proficiency testing in interlaboratory surveys. This generic type of device includes controls (assayed and unassayed) for blood gases, electrolytes, enzymes, multianalytes (all kinds), single (specified) analytes, or urinalysis controls.(b)
Classification. Class I (general controls). Except when intended for use in donor screening tests, quality control materials (assayed and unassayed) are exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.